In recent years, it has been demonstrated repeatedly that there is little tangible improvement in clinical outcomes from performing acute hemodynamic optimization of paced pulse timing. There is a reason for this. Since the heart is not a fatigable muscle, a hemodynamic sensor by itself gives no indication if a pacing intervention improves hemodynamics at the expense of greater energy expenditure, which could trigger maladaptive neurohormonal mechanisms within minutes to hours, or if the pacing intervention truly unloads the left ventricle.
The goal of cardiac resynchronization therapy (CRT) is to synchronize mechanical activation, which can relieve compensatory mechanisms and unload the heart. Preload (the force of blood that fills the left ventricle) and afterload (the force against which the left ventricle must work to eject blood) are the two factors that determine cardiac output, in addition to the force of contraction. Increasing preload is a mechanism used by the body to compensate for poor cardiac function. Though there is some nonlinearity in the pressure-volume preload relationship, maintaining higher filling pressure allows a greater volume of blood to fill the left ventricle.
In particular, the Frank-Starling law explains how preload helps to maintain cardiac output (CO). The curves shown in FIG. 1 are used to illustrate a relationship between preload and CO. In FIG. 1, preload is indicated by left ventricular end-diastolic pressure (LV EDP), which is closely related to the left atrial pressure (LAP) when blood enters the left ventricle during diastolic filling. The curves at the left in FIG. 1 show different possible Frank-Starling curves as a function of contractility. The curves at the right in FIG. 1 show different Frank-Starling curves and as a function of afterload, expressed as arterial resistance. In advanced heart failure (HF), a curve may even have a negative slope at elevated filling pressure.
Still referring to FIG. 1, the Frank-Starling curves show CO as a function of LV EDP, where LV EDP is a surrogate of preload. All of the curves show that increasing preload leads to an increase in CO, which may not be true in advanced HF. At the left, the curves demonstrate that higher contractility can also increase CO. At the right, the curves show that higher afterload (expressed by arterial resistance) reduces CO.
Except in extreme deterioration, such as decompensated HF, the body's powerful neurohormonal mechanisms compensate in various ways to maintain CO. Even if a sub-optimal pacing configuration is programmed, the body attempts to preserve CO. Some of these adaptations are considered hallmark signs of HF, such as an increase in resting heart rate and over-activation of the renin-angiotensin-aldosterone system. It may be less easily measured, but is certainly no less important, that the body may decrease the amount of blood distributed to organs of the body to accumulate blood and maintain a higher filling pressure in an attempt to compensate for poor cardiac function. When all other factors are kept unchanged, the ventricles will be able to expel a greater amount of blood during systole if the force bringing blood into the ventricles during diastole is greater.
Thus, it may be concluded that the acute change in CO caused by activating a pacing intervention has an unclear relationship to the outcome that will result from long-term use of the pacing intervention. Acute CO changes are, rather, a measure of the delay to action of the body's compensatory mechanisms. Similarly, it is likely that there will be neither a clear acute change in LAP morphology, nor even in its mean value over the cardiac cycle, immediately after starting a pacing intervention.